The purpose of this study is to evaluate plasma levels of hepatotoxic anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide plus significant metabolites) among patients on antituberculosis treatment (ATT) and compare the same among those who develop drug induced hepatitis on follow up versus those who do not.

Cases - those patients who develop DIH while on regular treatment with anti-TB drugs.

Controls - patients who do not develop DIH while on regular treatment with anti-TB drugs.

Detailed Description:

Tuberculosis (TB) is a major health problem in both the developing and developed countries because of its resurgence in the immunosuppressed patients. World Health Organization (WHO) in 1993 declared tuberculosis to be a 'global emergency' with more than a third of the world's population infected. Globally 8.9 million new cases of tuberculosis occur annually, of which 1.8 million (20%) occur in India.

Short-course chemotherapy containing isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) has proved to be highly effective in the treatment of tuberculosis. One of its adverse effects is hepatotoxicity. It is the most common side effect leading to interruption of therapy. It is associated with mortality of 6-12% if these drugs are continued even after the onset of symptoms. Risk of hepatotoxicity is increased when these drugs are combined.

The time interval between the start of anti-TB drugs and appearance of hepatotoxicity varies from 3 to 135 days. In most cases hepatitis is evident within three months of start of antituberculosis treatment (ATT).

The pathogenesis of drug-induced hepatotoxicity (DIH) is still not entirely clear for most anti TB drugs including rifampicin. Hypersensitivity is a definite possibility Rifampicin induced hepatitis has been postulated to occur as a part of systemic allergic reaction and, due to unconjugated hyperbilirubinaemia as a result of competition with bilirubin for uptake at hepatocyte plasma membrane. DIH caused by rifampicin occurs earlier as compared to isoniazid. While a dose related toxicity may exist, a direct correlation between serum drug levels and hepatotoxicity has not been well reported. Thus the clinical relevance of therapeutic monitoring of serum rifampicin concentrations in managing DIH is still being explored.

Present study done to observe serum rifampicin, isoniazid, pyrazinamide level in patients on ATT and to compare it retrospectively between patients who develop drug induced hepatitis vs those who do not.

Eligibility

Ages Eligible for Study:

16 Years to 65 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Sampling Method:

Non-Probability Sample

Study Population

Subjects: Patients with diagnosis of CatI/CatIII Tuberculosis attending the out-patient department of the All India Institute of Medical Sciences, New Delhi, will form the study population.

Cases - those patients who develop DIH while on regular treatment with anti-TB drugs Controls - age, sex matched patients who do not develop DIH while on regular treatment with anti-TB drugs

Criteria

Inclusion Criteria:

Patients diagnosed to be suffering from CatI/CatIII tuberculosis by a physician

Chronic alcoholics who consume > 48 g of alcohol/day for at least one year

Pregnant women

Subjects not willing to participate

Known patients with malabsorption or drug abuse

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00929786